The present invention is concerned with the materials and methods for constructing "micellar nanoparticles," micelle-like particles with mean diameters less than 1000 nanometers (one micron). These micellar nanoparticles are submicron-sized, oil-based particles, the smallest of which are filterable through a 0.2 micron filter such as is standardly used for microbiological purification. The micellar nanoparticles of the invention may be formed into stable dispersions in aqueous solutions and buffers.
The micellar nanoparticles have a variety of uses because of their small size. Other synthetic particles such as liposomes, nonphospholipid lipid vesicles and microcapsules are normally a micron or larger. In contrast, it is possible to form the micellar nanoparticles of the invention in sizes less than 100 nanometers diameter. Unlike lipid vesicles, some of which can be engineered to carry an oil, see, e.g., U.S. Pat. No. 4,911,928 to Wallach, the present particles require at least an oil, a stabilizer/surfactant, an initiator, and water or another diluent in their manufacture. However, neither cholesterol nor phospholipids are used. In fact, these nanoparticles can be made using food grade, USP or NF grade materials suitable for human use applications. This is particularly important if these micellar nanoparticles are to be used for topical delivery of a material into the bloodstream. One specific use of this type of system is the delivery of natural or synthetic hormones such as estradiol. These materials often have solubility problems; e.g., they are often only soluble in materials such as ethanol which can be difficult to incorporate in stable particulate systems.
Micellar nanoparticles are unique in that they allow materials that are soluble in any of water, oil, or the initiator (i.e., ethanol or methanol) to be incorporated into stable particles with mean diameters between about 30 and 1000 nanometers. Most preparations have particle diameters between 30 to 500 nanometers, are mixable in water, and filterable through either 0.2 or 0.45 micron filters. They can be stored at between -20 and 25 degrees C.degree..
Utilizing the materials and methods describe, one can produce micellar nanoparticles that do the following:
1. Incorporate ethanol or methanol soluble drugs into the particles.
2. Incorporate ethanol or methanol soluble pesticides into the particles.
3. Incorporate adjuvants into the particles.
4. Incorporate proteins into the particles.
5. Incorporate whole viruses containing intact nucleic acids into the particles. It must be noted, however, that the smaller particles of the invention are about the same size as many viruses.
6. Incorporate ethanol-extracted flavors into the particles.
7. Incorporate volatile oils (flavors and fragrances) into the particles.
8. Incorporate a charge into the particles.
9. Create colored particles.
Of particular importance is the ability to transmit drugs topically. It has been known for many years that small particles, such as those below one micron in diameter, can more easily traverse the skin boundary than larger particles. However, the small amount of drug transmitted in small particles has often limited their usefulness In addition, most particles have only had limited classes of materials they could deliver.
Accordingly, an object of the invention is to produce submicron particles which can deliver a variety of classes of materials.
Another object of the invention is to produce submicron particles that can deliver materials that are soluble in ethanol or methanol but have limited or no solubility in aqueous and oil systems.
A further object of the invention is to produce particles below 100 nanometers in diameter that can be used for drug delivery.
A still further object of the invention is to produce a particle for topical delivery of hormones such as estradiol.
These and other objects and features of the invention will be apparent from the description and the claims.